Cytotoxic Effect of S-Petasin and Iso-S-Petasin on the Proliferation of Human Prostate Cancer Cells

BACKGROUND: Petasin (Petasides hybridus) is a perennial shrub that is found in Europe as well as parts of Asia and North America and is being used to treat hypertension, tumors and asthma. In a previous study, we reported that petasin possesses biological effects including inhibition of testosterone production and the release of corticosterone from rat zona fasciculata-reticularis cells, and anti-proliferative effect on human T24 bladder carcinoma cells. MATERIALS AND METHODS: In the present study, we assessed the effects of S-petasin and iso-S-petasin on the growth and proliferation of two hormone-independent DU145 and PC3 and one hormone-dependent LNCaP prostate cancer cell line at concentrations of 10(-7)-10(-5) mol/l. The cell proliferation index, cell number index, expression of caspases and apoptosis-associated proteins and cell morphology were measured. RESULTS: S-Petasin and iso-S-petasin reduced the viable cell number and increased the numbers of apoptotic cells in the tested cell lines in a dose-dependent manner. Western blot analysis revealed that S-petasin and iso-S-petasin reduced the protein levels of procaspase 3, 8, and 9 and cleaved poly(ADP-ribose) polymerase (PARP) in all tested prostate cancer cell lines, and reduced that of procaspase 7 in LNCaP and PC3 cells. At the same time, S-petasin and iso-S-petasin increased mitochondrial membrane permeability and cytochrome c release from mitochondria to the cytosol via reducing the ratio of BCL2/BAX in DU145 and PC3 cells, and up-regulating the levels of p53 in DU145 cells but down-regulating it in PC3 cells. CONCLUSION: These results indicate that S-petasin and iso-S-petasin induce apoptosis via the activation of mitochondria-related pathways in prostate cancer cells, suggesting S-petasin and iso-S-petasin could be potential anticancer agents.